Efficacy and Safety of an Ad26.RSV.preF-RSV preF Protein Vaccine in Older Adults.

Aged Humans Antibodies, Neutralizing / blood Antibodies, Viral / blood Double-Blind Method Respiratory Syncytial Virus Infections / blood Respiratory Syncytial Virus Vaccines / adverse effects Respiratory Syncytial Virus, Human / immunology Respiratory Tract Infections / blood Vaccine Efficacy Immunogenicity, Vaccine / immunology Treatment Outcome

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
16 02 2023
Historique:
entrez: 15 2 2023
pubmed: 16 2 2023
medline: 18 2 2023
Statut: ppublish

Résumé

Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease in older adults, but no licensed RSV vaccine currently exists. An adenovirus serotype 26 RSV vector encoding a prefusion F (preF) protein (Ad26.RSV.preF) in combination with RSV preF protein was previously shown to elicit humoral and cellular immunogenicity. We conducted a randomized, double-blind, placebo-controlled, phase 2b, proof-of-concept trial to evaluate the efficacy, immunogenicity, and safety of an Ad26.RSV.preF-RSV preF protein vaccine. Adults who were 65 years of age or older were randomly assigned in a 1:1 ratio to receive vaccine or placebo. The primary end point was the first occurrence of RSV-mediated lower respiratory tract disease that met one of three case definitions: three or more symptoms of lower respiratory tract infection (definition 1), two or more symptoms of lower respiratory tract infection (definition 2), and either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom (definition 3). Overall, 5782 participants were enrolled and received an injection. RSV-mediated lower respiratory tract disease meeting case definitions 1, 2, and 3 occurred in 6, 10, and 13 vaccine recipients and in 30, 40, and 43 placebo recipients, respectively. Vaccine efficacy was 80.0% (94.2% confidence interval [CI], 52.2 to 92.9), 75.0% (94.2% CI, 50.1 to 88.5), and 69.8% (94.2% CI, 43.7 to 84.7) for case definitions 1, 2, and 3, respectively. After vaccination, RSV A2 neutralizing antibody titers increased by a factor of 12.1 from baseline to day 15, a finding consistent with other immunogenicity measures. Percentages of participants with solicited local and systemic adverse events were higher in the vaccine group than in the placebo group (local, 37.9% vs. 8.4%; systemic, 41.4% vs. 16.4%); most adverse events were mild to moderate in severity. The frequency of serious adverse events was similar in the vaccine group and the placebo group (4.6% and 4.7%, respectively). In adults 65 years of age or older, Ad26.RSV.preF-RSV preF protein vaccine was immunogenic and prevented RSV-mediated lower respiratory tract disease. (Funded by Janssen Vaccines and Prevention; CYPRESS ClinicalTrials.gov number, NCT03982199.).

Sections du résumé

BACKGROUND
Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease in older adults, but no licensed RSV vaccine currently exists. An adenovirus serotype 26 RSV vector encoding a prefusion F (preF) protein (Ad26.RSV.preF) in combination with RSV preF protein was previously shown to elicit humoral and cellular immunogenicity.
METHODS
We conducted a randomized, double-blind, placebo-controlled, phase 2b, proof-of-concept trial to evaluate the efficacy, immunogenicity, and safety of an Ad26.RSV.preF-RSV preF protein vaccine. Adults who were 65 years of age or older were randomly assigned in a 1:1 ratio to receive vaccine or placebo. The primary end point was the first occurrence of RSV-mediated lower respiratory tract disease that met one of three case definitions: three or more symptoms of lower respiratory tract infection (definition 1), two or more symptoms of lower respiratory tract infection (definition 2), and either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom (definition 3).
RESULTS
Overall, 5782 participants were enrolled and received an injection. RSV-mediated lower respiratory tract disease meeting case definitions 1, 2, and 3 occurred in 6, 10, and 13 vaccine recipients and in 30, 40, and 43 placebo recipients, respectively. Vaccine efficacy was 80.0% (94.2% confidence interval [CI], 52.2 to 92.9), 75.0% (94.2% CI, 50.1 to 88.5), and 69.8% (94.2% CI, 43.7 to 84.7) for case definitions 1, 2, and 3, respectively. After vaccination, RSV A2 neutralizing antibody titers increased by a factor of 12.1 from baseline to day 15, a finding consistent with other immunogenicity measures. Percentages of participants with solicited local and systemic adverse events were higher in the vaccine group than in the placebo group (local, 37.9% vs. 8.4%; systemic, 41.4% vs. 16.4%); most adverse events were mild to moderate in severity. The frequency of serious adverse events was similar in the vaccine group and the placebo group (4.6% and 4.7%, respectively).
CONCLUSIONS
In adults 65 years of age or older, Ad26.RSV.preF-RSV preF protein vaccine was immunogenic and prevented RSV-mediated lower respiratory tract disease. (Funded by Janssen Vaccines and Prevention; CYPRESS ClinicalTrials.gov number, NCT03982199.).

Identifiants

DOI: 10.1056/NEJMoa2207566 PMID: 36791161
pubmed: 36791161
doi: 10.1056/NEJMoa2207566
doi:

Substances chimiques

Antibodies, Neutralizing 0
Antibodies, Viral 0
Respiratory Syncytial Virus Vaccines 0

Banques de données

ClinicalTrials.gov
['NCT03982199']

Types de publication

Clinical Trial, Phase II Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

609-620

Investigateurs

Mohammed Allaw (M)
Toby Briskin (T)
Daniel Brune (D)
Richard Egelhof (R)
John Ervin (J)
Ann Falsey (A)
Carolos Fierro (C)
David Fried (D)
Peta-Gay Jackson-Booth (PG)
Murray Kimmel (M)
Lorrie McGill (L)
Paul Nugent (P)
Suchet Patel (S)
Barbara Rizzardi (B)
James Ruhlmann (J)
Cynthia Strout (C)
Leslie Tharenos (L)
Timothy Vachris (T)
Tyler Wadsworth (T)

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2023 Massachusetts Medical Society.

Auteurs

Ann R Falsey (AR)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Kristi Williams (K)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Efi Gymnopoulou (E)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Stephan Bart (S)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

John Ervin (J)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Arangassery R Bastian (AR)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Joris Menten (J)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Els De Paepe (E)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Sjouke Vandenberghe (S)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Eric K H Chan (EKH)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Jerald Sadoff (J)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Macaya Douoguih (M)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Benoit Callendret (B)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Christy A Comeaux (CA)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

Esther Heijnen (E)

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Efficacy and Safety of an Ad26.RSV.preF-RSV...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Efficacy and Safety of an Ad26.RSV.preF-RSV...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps neutralisants › Efficacy and Safety of an Ad26.RSV.preF-RSV...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antiviraux › Efficacy and Safety of an Ad26.RSV.preF-RSV...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › Efficacy and Safety of an Ad26.RSV.preF-RSV...
questionsmedicales.fr › Infection › Maladies virales › Infections à virus à ARN › Infections à Mononegavirales › Infections à Paramyxoviridae › Infections à pneumovirus › Infections à virus respiratoire syncytial › Efficacy and Safety of an Ad26.RSV.preF-RSV...
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Vaccins › Vaccins antiviraux › Vaccins contre les virus respiratoires syncytiaux › Efficacy and Safety of an Ad26.RSV.preF-RSV...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN de polarité négative › Mononegavirales › Paramyxoviridae › Pneumovirinae › Pneumovirus › Virus respiratoires syncytiaux › Virus respiratoire syncytial humain › Efficacy and Safety of an Ad26.RSV.preF-RSV...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Efficacy and Safety of an Ad26.RSV.preF-RSV...
questionsmedicales.fr › Techniques d'investigation › Développement de vaccin › Efficacité vaccinale › Efficacy and Safety of an Ad26.RSV.preF-RSV...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunogénicité des vaccins › Efficacy and Safety of an Ad26.RSV.preF-RSV...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Efficacy and Safety of an Ad26.RSV.preF-RSV...